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PMID:16753195,9851930,11607032
For example, lipopolysaccharide (LPS), a common structure of the cell wall of Gram-negative bacteria, is recognized by TLR4 ; double-stranded RNA (dsRNA), which has long been considered a viral PAMP, triggers TLR3 signaling

PMID: 16753195,9851930
LPS has long been identified as ligand for TLR4 via analysis of mice with a point mutation in the gene encoding TLR4 </csml:comment>
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PMID:16753195,9851930,11607032
For example, lipopolysaccharide (LPS), a common structure of the cell wall of Gram-negative bacteria, is recognized by TLR4 ; double-stranded RNA (dsRNA), which has long been considered a viral PAMP, triggers TLR3 signaling</csml:comment>
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PMID: 16753195,15229469,15207506
Natural or synthetic oligodeoxynucleotides (OND) containing an unmethylated CpG motif (CpG) can activate TLR9, which exclusively couples to the MyD88-dependent pathway</csml:comment>
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PMID: 16753195
Upon stimulation of TLRs, MyD88 is recruited to the TIR domain of TLRs.</csml:comment>
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PMID: 16753195
MyD88 further recruits IRAK4 to form TLR&#8211;MyD88&#8211;IRAK4 signal complex.</csml:comment>
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pMID: 16753195
Then the signal complex (TLR&#8211;MyD88&#8211;IRAK4) recruits IRAK1 and thereby phosphorylates and activates it. </csml:comment>
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pMID: 16753195
Then the signal complex (TLR&#8211;MyD88&#8211;IRAK4) recruits IRAK1 and thereby phosphorylates and activates it. </csml:comment>
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PMID: 16753195
The activated IRAK1 autophosphorylates residues in its N-terminus, which leads to recruitment and binding of TRAF6 to the receptor signaling complex</csml:comment>
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PMID: 16753195
The activated IRAK1 autophosphorylates residues in its N-terminus, which leads to recruitment and binding of TRAF6 to the receptor signaling complex</csml:comment>
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PMID: 16753195,15229469
The IRAK1&#8211;TRAF6 complex then disassociates from the receptor and interacts with another complex consisting of TAK1, TAB1 and TAB2, followed by the phosphorylation and activation of TAK1 </csml:comment>
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PMID: 16753195,15229469
The IRAK1&#8211;TRAF6 complex then disassociates from the receptor and interacts with another complex consisting of TAK1, TAB1 and TAB2, followed by the phosphorylation and activation of TAK1 </csml:comment>
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PMID: 16753195,15229469
The IRAK1&#8211;TRAF6 complex then disassociates from the receptor and interacts with another complex consisting of TAK1, TAB1 and TAB2, followed by the phosphorylation and activation of TAK1 </csml:comment>
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PMID: 16753195,15229469
The IRAK1&#8211;TRAF6 complex then disassociates from the receptor and interacts with another complex consisting of TAK1, TAB1 and TAB2, followed by the phosphorylation and activation of TAK1 </csml:comment>
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PMID: 16753195
The activated TAK1 subsequently activates the I&#954;B kinases (IKKs), which phosphorylates I&#954;B and leads to activation of NF-&#954;B. 
</csml:comment>
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PMID: 16753195
The activated TAK1 subsequently activates the I&#954;B kinases (IKKs), which phosphorylates I&#954;B and leads to activation of NF-&#954;B. 
</csml:comment>
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PMID: 16753195
The activated TAK1 subsequently activates the I&#954;B kinases (IKKs), which phosphorylates I&#954;B and leads to activation of NF-&#954;B. 
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PMID: 16753195,10094049,16186825,15229469
Activation of TAK1 also results in the activation of MAPKs, including c-Jun N-terminal kinase (JNK), leading to activation of AP-1</csml:comment>
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PMID: 16753195,10094049,16186825,15229469
Activation of TAK1 also results in the activation of MAPKs, including c-Jun N-terminal kinase (JNK), leading to activation of AP-1</csml:comment>
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PMID: 16753195,11058605,11385577,12527755,12766759,12514169
There is evidence that NOD1 and NOD2 can recognize the core structures of bacterial peptidoglycan in the cytoplasm to activate NF-&#954;B, which is TLR independent</csml:comment>
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PMID: 16753195,11058605,11385577,12527755,12766759,12514169
There is evidence that NOD1 and NOD2 can recognize the core structures of bacterial peptidoglycan in the cytoplasm to activate NF-&#954;B, which is TLR independent</csml:comment>
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PMID: 16753195,11058605,11385577,12527755,12766759,12514169
There is evidence that NOD1 and NOD2 can recognize the core structures of bacterial peptidoglycan in the cytoplasm to activate NF-&#954;B, which is TLR independent</csml:comment>
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PMID: 16753195,11058605,11385577,12527755,12766759,12514169
There is evidence that NOD1 and NOD2 can recognize the core structures of bacterial peptidoglycan in the cytoplasm to activate NF-&#954;B, which is TLR independent</csml:comment>
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PMID: 16753195
Recently, it has been shown that two cytoplasmic RNA helicase proteins, Mda-5 and RIG-I, are sensors of viral dsRNA, which initiate antiviral responses via the adaptor protein VISA/IPS-1/MAVS/Cardif</csml:comment>
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PMID: 16753195
Recently, it has been shown that two cytoplasmic RNA helicase proteins, Mda-5 and RIG-I, are sensors of viral dsRNA, which initiate antiviral responses via the adaptor protein VISA/IPS-1/MAVS/Cardif</csml:comment>
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PMID: 16753195
Recently, it has been shown that two cytoplasmic RNA helicase proteins, Mda-5 and RIG-I, are sensors of viral dsRNA, which initiate antiviral responses via the adaptor protein VISA/IPS-1/MAVS/Cardif</csml:comment>
</csml:comments>
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PMID: 16753195,16143103
More recently, it was shown that the glucocorticoid receptor (GR) can selectively transrepress the transcription of a subset of genes (such as Scyb9), of which promoters utilize IRF3 as an essential coactivator of NF-&#954;B binding to the &#954;B sites upon LPS stimulation</csml:comment>
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PMID: 16753195,16143103
More recently, it was shown that the glucocorticoid receptor (GR) can selectively transrepress the transcription of a subset of genes (such as Scyb9), of which promoters utilize IRF3 as an essential coactivator of NF-&#954;B binding to the &#954;B sites upon LPS stimulation</csml:comment>
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indirect</csml:comment>
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<csml:comment type="text">


PMID: 16753195,16143103
For example, both dsRNA and LPS can activate transcription of the IP10 gene</csml:comment>
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indirect</csml:comment>
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PMID: 16753195,16143103
For example, both dsRNA and LPS can activate transcription of the IP10 gene</csml:comment>
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PMID: 16753195,15229469,15733829
TLR3 signals through myeloid differentiation primary response protein-88 (MyD88)-independent and Toll/interleukin receptor (TIR) domain-containing adaptor-inducing IFN-&#946; (TRIF, also known as TICAM-1)-dependent pathways</csml:comment>
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PMID: 16753195
The adaptor protein TRIF has been demonstrated to interact with the TRAF family-member-associated NF-&#954;B activator (TANK) binding kinase 1 (TBK1) and IKK&#949; (also known as IKKi) as well as IRF3/7 and thereby to facilitate TBK1 and IKK&#949; to phosphorylate and activate IRF3/7.</csml:comment>
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PMID: 16753195
The adaptor protein TRIF has been demonstrated to interact with the TRAF family-member-associated NF-&#954;B activator (TANK) binding kinase 1 (TBK1) and IKK&#949; (also known as IKKi) as well as IRF3/7 and thereby to facilitate TBK1 and IKK&#949; to phosphorylate and activate IRF3/7.</csml:comment>
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PMID: 16753195,14739303,16153868
Besides IKK&#949; and TBK1, TRAF6, IKK&#946; and receptor&#8211;interactor protein-1 (RIP1) also interact with TRIF</csml:comment>
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<csml:comments>
<csml:comment type="text">


PMID: 16753195,14739303,16153868
Besides IKK&#949; and TBK1, TRAF6, IKK&#946; and receptor&#8211;interactor protein-1 (RIP1) also interact with TRIF</csml:comment>
</csml:comments>
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<csml:comments>
<csml:comment type="text">


indirect</csml:comment>
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</csml:comment>
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<csml:comment type="text">


PMID: 16753195
The adaptor protein TRIF has been demonstrated to interact with the TRAF family-member-associated NF-&#954;B activator (TANK) binding kinase 1 (TBK1) and IKK&#949; (also known as IKKi) as well as IRF3/7 and thereby to facilitate TBK1 and IKK&#949; to phosphorylate and activate IRF3/7.</csml:comment>
</csml:comments>
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indirect</csml:comment>
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</csml:comment>
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<csml:comment type="text">


PMID: 16753195
The adaptor protein TRIF has been demonstrated to interact with the TRAF family-member-associated NF-&#954;B activator (TANK) binding kinase 1 (TBK1) and IKK&#949; (also known as IKKi) as well as IRF3/7 and thereby to facilitate TBK1 and IKK&#949; to phosphorylate and activate IRF3/7.</csml:comment>
</csml:comments>
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<csml:comment type="text">


indirect</csml:comment>
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<csml:comments>
<csml:comment type="text">


PMID: 16753195
The adaptor protein TRIF has been demonstrated to interact with the TRAF family-member-associated NF-&#954;B activator (TANK) binding kinase 1 (TBK1) and IKK&#949; (also known as IKKi) as well as IRF3/7 and thereby to facilitate TBK1 and IKK&#949; to phosphorylate and activate IRF3/7.</csml:comment>
</csml:comments>
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<csml:comments>
<csml:comment type="text">


indirect</csml:comment>
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PMID: 16753195
The adaptor protein TRIF has been demonstrated to interact with the TRAF family-member-associated NF-&#954;B activator (TANK) binding kinase 1 (TBK1) and IKK&#949; (also known as IKKi) as well as IRF3/7 and thereby to facilitate TBK1 and IKK&#949; to phosphorylate and activate IRF3/7.</csml:comment>
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PMID: 16753195
Recently, it has been shown that two cytoplasmic RNA helicase proteins, Mda-5 and RIG-I, are sensors of viral dsRNA, which initiate antiviral responses via the adaptor protein VISA/IPS-1/MAVS/Cardif</csml:comment>
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PMID: 16753195,12721283,14519765,14993454,15229469
In addition, two other adaptors, TIR-containing adaptor protein (TIRAP, also known as Mal) and TIR-containing protein (TIRP, also known as TRAM and TICAM-2), participate in those two pathways, respectively</csml:comment>
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PMID: 16753195
TLR4 makes use of both TRIF and MyD88 adaptors to activate IRF3/7, NF-&#954;B and AP-1 upon the stimulation of LPS.</csml:comment>
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PMID: 16753195
The adaptor protein TRIF has been demonstrated to interact with the TRAF family-member-associated NF-&#954;B activator (TANK) binding kinase 1 (TBK1) and IKK&#949; (also known as IKKi) as well as IRF3/7 and thereby to facilitate TBK1 and IKK&#949; to phosphorylate and activate IRF3/7.</csml:comment>
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PMID: 16753195
The adaptor protein TRIF has been demonstrated to interact with the TRAF family-member-associated NF-&#954;B activator (TANK) binding kinase 1 (TBK1) and IKK&#949; (also known as IKKi) as well as IRF3/7 and thereby to facilitate TBK1 and IKK&#949; to phosphorylate and activate IRF3/7.</csml:comment>
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PMID: 16753195,14739303,16153868
Besides IKK&#949; and TBK1, TRAF6, IKK&#946; and receptor&#8211;interactor protein-1 (RIP1) also interact with TRIF</csml:comment>
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PMID: 16753195,14739303,16153868
Besides IKK&#949; and TBK1, TRAF6, IKK&#946; and receptor&#8211;interactor protein-1 (RIP1) also interact with TRIF</csml:comment>
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PMID: 16753195,14739303,16153868
Besides IKK&#949; and TBK1, TRAF6, IKK&#946; and receptor&#8211;interactor protein-1 (RIP1) also interact with TRIF</csml:comment>
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indirect</csml:comment>
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<csml:comment type="text">


PMID: 16753195
The adaptor protein TRIF has been demonstrated to interact with the TRAF family-member-associated NF-&#954;B activator (TANK) binding kinase 1 (TBK1) and IKK&#949; (also known as IKKi) as well as IRF3/7 and thereby to facilitate TBK1 and IKK&#949; to phosphorylate and activate IRF3/7.</csml:comment>
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indirect</csml:comment>
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PMID: 16753195
The adaptor protein TRIF has been demonstrated to interact with the TRAF family-member-associated NF-&#954;B activator (TANK) binding kinase 1 (TBK1) and IKK&#949; (also known as IKKi) as well as IRF3/7 and thereby to facilitate TBK1 and IKK&#949; to phosphorylate and activate IRF3/7.</csml:comment>
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indirect</csml:comment>
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<csml:comment type="text">


PMID: 16753195
The adaptor protein TRIF has been demonstrated to interact with the TRAF family-member-associated NF-&#954;B activator (TANK) binding kinase 1 (TBK1) and IKK&#949; (also known as IKKi) as well as IRF3/7 and thereby to facilitate TBK1 and IKK&#949; to phosphorylate and activate IRF3/7.</csml:comment>
</csml:comments>
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indirect</csml:comment>
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<csml:comment type="text">


PMID: 16753195
The adaptor protein TRIF has been demonstrated to interact with the TRAF family-member-associated NF-&#954;B activator (TANK) binding kinase 1 (TBK1) and IKK&#949; (also known as IKKi) as well as IRF3/7 and thereby to facilitate TBK1 and IKK&#949; to phosphorylate and activate IRF3/7.</csml:comment>
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PMID: 16753195,16127453,16153868
For instance, VISA forms a complex with FADD and RIP1 , and it also interacts with TRAF6 in our study</csml:comment>
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PMID: 16753195,16127453,16153868
For instance, VISA forms a complex with FADD and RIP1 , and it also interacts with TRAF6 in our study</csml:comment>
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PMID: 16753195,12721283,14519765,14993454,15229469
In addition, two other adaptors, TIR-containing adaptor protein (TIRAP, also known as Mal) and TIR-containing protein (TIRP, also known as TRAM and TICAM-2), participate in those two pathways, respectively</csml:comment>
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PMID: 16753195
Upon stimulation of TLRs, MyD88 is recruited to the TIR domain of TLRs.</csml:comment>
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PMID: 16753195
MyD88 further recruits IRAK4 to form TLR&#8211;MyD88&#8211;IRAK4 signal complex.</csml:comment>
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pMID: 16753195
Then the signal complex (TLR&#8211;MyD88&#8211;IRAK4) recruits IRAK1 and thereby phosphorylates and activates it. </csml:comment>
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pMID: 16753195
Then the signal complex (TLR&#8211;MyD88&#8211;IRAK4) recruits IRAK1 and thereby phosphorylates and activates it. </csml:comment>
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PMID: 16753195
The activated IRAK1 autophosphorylates residues in its N-terminus, which leads to recruitment and binding of TRAF6 to the receptor signaling complex</csml:comment>
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PMID: 16753195
The activated IRAK1 autophosphorylates residues in its N-terminus, which leads to recruitment and binding of TRAF6 to the receptor signaling complex</csml:comment>
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PMID: 16753195,15229469
The IRAK1&#8211;TRAF6 complex then disassociates from the receptor and interacts with another complex consisting of TAK1, TAB1 and TAB2, followed by the phosphorylation and activation of TAK1 </csml:comment>
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indirect</csml:comment>
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PMID: 16753195
Both the RIP1/FADD and the TRAF6/TAK1 pathways are sufficient to activate NF-&#954;B.</csml:comment>
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PMID: 16753195
Both the RIP1/FADD and the TRAF6/TAK1 pathways are sufficient to activate NF-&#954;B.</csml:comment>
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PMID: 16753195,16127453,16153868
For instance, VISA forms a complex with FADD and RIP1 , and it also interacts with TRAF6 in our study</csml:comment>
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PMID: 16753195,16127453,16153868
For instance, VISA forms a complex with FADD and RIP1 , and it also interacts with TRAF6 in our study</csml:comment>
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PMID: 16753195
Both the RIP1/FADD and the TRAF6/TAK1 pathways are sufficient to activate NF-&#954;B.</csml:comment>
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indirect</csml:comment>
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PMID: 16753195
Both the RIP1/FADD and the TRAF6/TAK1 pathways are sufficient to activate NF-&#954;B.</csml:comment>
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PMID: 16753195
Both the RIP1/FADD and the TRAF6/TAK1 pathways are sufficient to activate NF-&#954;B.</csml:comment>
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indirect</csml:comment>
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PMID: 16753195
Both the RIP1/FADD and the TRAF6/TAK1 pathways are sufficient to activate NF-&#954;B.</csml:comment>
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PMID: 16753195,15064760,16115877
However, there also exist some distinct explanations about the involvement of RIP1 in TRIF-mediated NF-&#954;B activation. It has been suggested that TRIF interacts with RIP1, and this interaction mediates TLR3-triggered NF-&#954;B activation</csml:comment>
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PMID: 16753195
The TRIF-dependent pathway first stimulates activation of IRF3 leading to production of TNF alpha, which in turn triggers TNFR signaling to activate NF-&#954;B.

PMID: 16753195,16166516
By asking why the activation dynamics of NF-&#954;B show damped oscillatory behavior when cells are stimulated by tumor necrosis factor alpha (TNF alpha) but stable behavior when stimulated by LPS, however, proposed that the activation of NF-&#954;B by TRIF-dependent pathway is a result of a secondary response to TNF alpha, which is induced by IRF3 (activated by TLR4/TRIF-mediated pathway in the first response to LPS) and signals through TNF alpha receptor (TNFR)/RIP1 pathway to activate NF-&#954;B </csml:comment>
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PMID: 16753195
The TRIF-dependent pathway first stimulates activation of IRF3 leading to production of TNF alpha, which in turn triggers TNFR signaling to activate NF-&#954;B.

PMID: 16753195,16166516
By asking why the activation dynamics of NF-&#954;B show damped oscillatory behavior when cells are stimulated by tumor necrosis factor alpha (TNF alpha) but stable behavior when stimulated by LPS, however, proposed that the activation of NF-&#954;B by TRIF-dependent pathway is a result of a secondary response to TNF alpha, which is induced by IRF3 (activated by TLR4/TRIF-mediated pathway in the first response to LPS) and signals through TNF alpha receptor (TNFR)/RIP1 pathway to activate NF-&#954;B </csml:comment>
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PMID: 16753195
The TRIF-dependent pathway first stimulates activation of IRF3 leading to production of TNF alpha, which in turn triggers TNFR signaling to activate NF-&#954;B.

PMID: 16753195,16166516
By asking why the activation dynamics of NF-&#954;B show damped oscillatory behavior when cells are stimulated by tumor necrosis factor alpha (TNF alpha) but stable behavior when stimulated by LPS, however, proposed that the activation of NF-&#954;B by TRIF-dependent pathway is a result of a secondary response to TNF alpha, which is induced by IRF3 (activated by TLR4/TRIF-mediated pathway in the first response to LPS) and signals through TNF alpha receptor (TNFR)/RIP1 pathway to activate NF-&#954;B </csml:comment>
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PMID: 16753195
The TLR3 and TLR4 initiated signaling pathways converge at TRIF, which signals through IKK&#946;, IKK&#949; and/or TBK1 for activation of IRF3/7.</csml:comment>
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PMID: 16753195
The TLR3 and TLR4 initiated signaling pathways converge at TRIF, which signals through IKK&#946;, IKK&#949; and/or TBK1 for activation of IRF3/7.</csml:comment>
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PMID: 16753195
The TLR3 and TLR4 initiated signaling pathways converge at TRIF, which signals through IKK&#946;, IKK&#949; and/or TBK1 for activation of IRF3/7.</csml:comment>
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PMID: 16753195
The TLR3 and TLR4 initiated signaling pathways converge at TRIF, which signals through IKK&#946;, IKK&#949; and/or TBK1 for activation of IRF3/7.</csml:comment>
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PMID: 16753195
Stimulation of TLRs by PAMPs induces activation and translocation to nucleus of nuclear factor-&#954;B (NF-&#954;B), interferon regulatory factor 3/7 (IRF3/7) and/or activator protein-1 (AP-1), which collaborate to induce transcription of various cytokines such as alpha/beta interferon (IFN-alpha/beta), leading to clearance of the infectious pathogens.</csml:comment>
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PMID: 16753195
Stimulation of TLRs by PAMPs induces activation and translocation to nucleus of nuclear factor-&#954;B (NF-&#954;B), interferon regulatory factor 3/7 (IRF3/7) and/or activator protein-1 (AP-1), which collaborate to induce transcription of various cytokines such as alpha/beta interferon (IFN-alpha/beta), leading to clearance of the infectious pathogens.</csml:comment>
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PMID: 16753195
Stimulation of TLRs by PAMPs induces activation and translocation to nucleus of nuclear factor-&#954;B (NF-&#954;B), interferon regulatory factor 3/7 (IRF3/7) and/or activator protein-1 (AP-1), which collaborate to induce transcription of various cytokines such as alpha/beta interferon (IFN-alpha/beta), leading to clearance of the infectious pathogens.</csml:comment>
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PMID: 16753195
Stimulation of TLRs by PAMPs induces activation and translocation to nucleus of nuclear factor-&#954;B (NF-&#954;B), interferon regulatory factor 3/7 (IRF3/7) and/or activator protein-1 (AP-1), which collaborate to induce transcription of various cytokines such as alpha/beta interferon (IFN-alpha/beta), leading to clearance of the infectious pathogens.</csml:comment>
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